Emerging Targeted, Immunotherapeutic and Nanocarrier-Based Strategies in Triple-Negative Breast Cancer: An Updated Review

Abstract

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor, progesterone receptor and HER2 expression and represents an aggressive and biologically heterogeneous breast cancer subtype. Historically, cytotoxic chemotherapy was the principal systemic treatment option. The therapeutic landscape has subsequently expanded through biomarker-directed strategies, immune checkpoint blockade, poly (ADP-ribose) polymerase (PARP) inhibition and antibody–drug conjugates (ADCs). Pembrolizumab-based therapy has become an established component of treatment for selected early-stage and PD-L1-positive advanced TNBC. PARP inhibitors provide an important option for patients with germline BRCA1/2 alterations, while ADCs have introduced target-directed delivery of potent cytotoxic payloads. The treatment landscape continued to evolve in 2026, including U.S. Food and Drug Administration approvals of datopotamab deruxtecan for selected unresectable or metastatic TNBC and first-line sacituzumab govitecan, alone or with pembrolizumab in PD-L1-positive disease. In parallel, nanocarrier-based systems—including liposomes, polymeric nanoparticles, albumin-bound nanoparticles, lipid nanoparticles, inorganic nanoparticles and exosome-based carriers—are being investigated to improve drug solubility, tumour accumulation, controlled release, co-delivery and modulation of the tumour immune microenvironment. However, translation remains limited by tumour heterogeneity, variable enhanced permeability and retention effects, resistance, toxicity, manufacturing complexity and regulatory requirements. This review summarizes the biology and clinical management of TNBC, recent targeted and immunotherapeutic advances, the evolving ADC landscape, nanocarrier-based strategies, mechanisms of treatment resistance, and priorities for future precision oncology research.

Keywords: Triple-negative breast cancer; PARP inhibitors; immune checkpoint inhibitors; antibody–drug conjugates; sacituzumab govitecan; datopotamab deruxtecan; nanocarriers; precision oncology; drug delivery; therapeutic resistance.